Patients with Symptomatic Primary Hyperparathyroidism: An Anaesthetic Challenge

Summary Primary hyperparathyroidismis a disease characterized by hypercalcaemiaattributable to autonomous overpro-duction of parathormone. Many patients with primary hyperparathyroidism are asymptomatic. Osteoporosis and nephrolithiasis are some of the major sequelae seen in the symptomatic patients. Parathyroidectomy is the only curative therapy. However anaesthetic management of such patients may be problematic with associated cardiac arrhythmias and skeletal muscleweakness. Low serum albumin and alteration in theacid base status in the perioperative period can affect the serum calcium level and thus adds to the existing problem. We present the successful anaesthetic management of a patient with primary hyperparathyroidism who initially presented with pathological fractures, and discuss the anaesthetic issues involved.


Introduction
Calcium plays a centralrole in a large number of physiological actions that are essentialfor life. Of particular relevance to the anaesthetist are the effects of calcium on the myocardium, vascular smooth muscle and blood coagulation. Theestimated incidence of hypercalcaemia is 1:1000 cases in males and 2-3:1000 cases in females, with primary hyperparathyroidism being the most common etiology. Primary hyperparathyroidism is the most common cause of hypercalcaemiain the outpatient setting, with manypatients being asymptomatic. Left undiagnosed, it can lead to severe complications of hyperparathyroidism suchas osteitis fibrosa cystica and nephrocalcinosis. 1 We describe the successfulanaesthetic managementof a patient with primary hyperparathyroidism who initially presented with pathologicalfractures.
She was diagnosed with pathological fracture of left sided neckof femur with healed fracture right neck of femur, for which she was put on bilateralskin traction. The patient was investigated for pathological fractures which revealed following results: serum calcium 11.8 mg/dl, serum parathormone 302.90 pg/ml (normal value15.0-68.30pg/ml), and alkaline phosphatase 2869 IU/l. Her serum electrolytes, blood urea, serum creatinine, albumin levels and electrocardiogram were within normallimits. Adiagnosis ofprimary hyperparathyroidism was made on the basis of hypercalcaemia with increased parathormonelevels. Ultrasound neckrevealed presence of a hypo echoic mass of 3×1.1×1.2 cm size just below the posteroinferioraspect of left lobe of thyroid. Technetium-99-m sestamibi parathyroid scan localized increased tracer uptake to posterior margin of left lobe of thyroid suggestive of left inferior parathyroid adenoma.
Once the diagnosis was confirmed,the patient was started on medical management with intravenous (IV) fluids and furosemide at dose of 40 mg IV 12 hourly. Subsequently her serum calcium came down to 8.2 mg/dl. Her hydration status and serum electro-lytes were monitored duringthis forced saline diuresis therapy. The patient was then placed for left parathyroidectomy. Preoperatively, the patientwas kept nil per orally after 10 pm. Premedication included ranitidine 150 mg, alprazolam 0.25mg orally night before and at 6a.m. on the morningof surgery.In theoperatingroom, intravenous access was secured the patient was connected to multichannelmonitor (S/5 Datex Ohmeda, Finland) and monitored for electrocardiogram (ECG), non-invasive blood pressure (NIBP), oxygen saturation, end tidal carbon dioxide (EtCO 2 ) and neuromuscular function. The patient was pre-oxygenated for 3 minutes, and anaesthesia was induced with IV morphine 4.5 mg and IV thiopentone sodium 250 mg. Vecuronium bromide 5 mg IV was administered to facilitatetrachealintubation.Anaesthesiawasmaintained with 66% nitrous oxide in oxygen and isoflurane 0.5-1%. Patient'sECG wascontinuously monitored to detect any change in cardiac rhythm due to altered calcium metabolism. Further boluses ofvecuronium bromide were given on the basis of neuromuscular monitoring. Patient's heart rate and blood pressure were stable throughout the period of surgery. End tidal CO 2 was maintained between 32 and 36 mmHg. The surgery lasted for 90 minutes during which she received 1.5 L of crystalloids. After completion of surgery, the residualparalysis was reversed with neostigmine and glycopyrrolate in dosages of 2mg and 0.4 mg respectively, with the guidance of neuromuscular monitor. During extubation the position of vocal cords was checked to assess any damage to recurrent laryngeal nerve. Intravenous calcium gluconate infusion was started slowly as a prophylactic measure and continued for 24 hours.
Postoperatively, the patient was kept in post anaesthesiacare unitand wasclosely observedfor signs and symptoms of hypocalcaemia. Serum calcium levels were checked regularly. On the second postoperative day, the patient was started on oral calcium. She received injectable paracetamoland tramadolfor postoperative pain control. Her postoperative course was uneventful. For the pathologicalfracture, thepatient was continued on skin traction and was discharged home with regular follow up at orthopaedics out patient department.
Manypatients withprimary hyperparathyroidism are asymptomatic. In symptomatic patients common findings include renalcalculi, bone pains, pathological fractures, skeletal muscle weakness or non-specific symptoms such as depression, lethargy, vague aches and pains. Cardiac manifestations include prolonged PR interval, short QTinterval and systemic hypertension. 2 The diagnosisof primaryhyperparathyroidism is demonstratedby persistenthypercalcaemia in the presence of normal or elevated parathyroid hormone concentration. 3,4 In our case, the patient presented with pathologicalfractures and bone pains. The patient was investigated for pathological fractures which subsequently demonstrated hypercalcaemia withprimary hyperparathyroidism.

Chopra Puneet et al. Patients with symptomatic primaryhyperparathyroidism: an anaesthetic challenge
tium-99 m sestamibi scan localized increased tracer activity in the left inferior parathyroid gland.
Primary hyperparathyroidism and the associated hypercalcaemia are treated initially by medical means followed by definitive surgicalremoval of the diseased or abnormal portions of parathyroid glands. Parathyroidectomy is the only curative treatment for primary hyperparathyroidism and is associated with 95% cure rate with minimal morbidity in the hands of an experienced endocrine surgeon. 6 Intravenous fluids are the initial therapy for severe hypercalcaemia. Diuretic therapy should not be initiated until euvolemia is achieved. Loop diuretics depress the proximal tubular reabsorption of calcium and can increase the urinary calcium excretion by 200-250 mEq/day. Thiazide diuretics are avoided as these drugs may enhance renal tubular reabsorption of calcium. The risks of forced d iu resis in clude cardiac decompensation, hy po ph osph ataemia, hypokalaemia and hypomagnesaemia.Other treatment modalities include antiresorptive agents such as bisphosphonates, calcitonin and dialysis, which are reserved for the patients with renal failure. 3,7 In our case, normocalcaemia was achieved with hydration andfurosemide therapy.
Although there are no specific guidelines for the conduct of anaesthesia in patients with primary hyperparathyroidism,anaesthesia for hyperparathyroidism is not without problems. One needs to be vigilant about various factors that might alter serum calcium levels. It is important to correct malnutrition and low albumin levels in the preoperative period. Preexisting hypertension, which is more common inprimary hyperparathyroidism, should be controlled if present. In the intraoperative period, special focus needs to be made on the acid base status and transfusion of large amounts of citrated blood, lest life threateninghypocalcaemia may ensue. 1 ContinuousECG monitoringin thesepatients is imperative as hypercalcaemia may be associated with disturbance in cardiac rhythm, although there is evidence that QTinterval may not be a reliable index of changes in serum calcium concentrationsduring anaesthesia. 8 Coexisting skeletalmuscle weakness may de-crease the requirement of muscle relaxant inthis group of patients. A reduction in the duration of action of rocuronium has been reported in a patient with normocalcaemic hyperparathyroidism, hence neuromuscular monitoringis mandatory, if available, in this group. 9 Our patient was also monitored for neuromuscular blockade, although there was no alteration in the duration ofaction ofmuscle relaxant.Acidosis decreases calcium bindingto albumin thusincreasing the levels of ionized calcium,which cancause life threatening hypercalcaemia,henceit isimportant tomaintain normocarbia. Our patient had severe osteoporosis and pathological fractures. This is apoint ofconcern while managing patients with hypercalcaemia.Positioningin the operating table thus needs special care in these patients. One of the serious complications in these patients is recurrent laryngealnerveinjury. Henceassessment of vocal cord movement duringextubation is imperative.Other severe problems encountered duringsurgery arebleeding and permanent hypoparathyroidism.Postoperative hypoparathyroidism needs to be monitored carefully.Ahigh index of suspicion may avert life threatening respiratory failure and concomitantECG changes.Serum calcium levelusually normalizes by 3 rd -4 th day andthus needs to be checked at regular postoperative intervals. 1-3 Patientswithprimary hyperparathyroidism usually develop less severe hypocalcaemia that is amenable to calcium therapyand itshould beroutinely initiatedfollowing subtotal parathyroidectomy. 10 Our patient received IV calcium gluconate infusion for the first 24 hours. Subsequently oralcalcium therapy was instituted. Further, in the postoperative period, non-steroidal anti-inflammatory drugs should be avoided for pain control in case there is renalfunction impairment. 1 In conclusion, it may be worth emphasizing that successful anaesthetic management of a patient with hyperparathyroidism requires vigilance for several factors that might potentiate adverse effects of hypo-and hypercalcaemia. These factors and their anaesthetic implications are summarized in Table 1.Adequate preoperative assessment and preparation, close monitoring of the signs and symptoms of hypo-and hypercalcaemia, restoration and keepingionized calcium within Table 1 Anaesthetic considerations in surgery for primary hyperparathyroidism.